![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 7, 3266-3284, July 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Obstetrics and Gynecology, and the Comparative and Experimental Medicine Program, Graduate School of Medicine, University of Tennessee, Knoxville, Tennessee 37920
Submitted November 17, 2003;
Revised April 16, 2004;
Accepted April 18, 2004
Monitoring Editor: Keith Yamamoto
Estrogens such as 17-
estradiol (E2) play a critical role in sporadic breast cancer progression and decrease apoptosis in breast cancer cells. Our studies using estrogen receptor-positive MCF7 cells show that E2 abrogates apoptosis possibly through phosphorylation/inactivation of the proapoptotic protein BAD, which was rapidly phosphorylated at S112 and S136. Inhibition of BAD protein expression with specific antisense oligonucleotides reduced the effectiveness of tumor necrosis factor-
, H2O2, and serum starvation in causing apoptosis. Furthermore, the ability of E2 to prevent tumor necrosis factor--induced apoptosis was blocked by overexpression of the BAD S112A/S136A mutant but not the wild-type BAD. BAD S112A/S136A, which lacks phosphorylation sites for p90RSK1 and Akt, was not phosphorylated in response to E2 in vitro. E2 treatment rapidly activated phosphatidylinositol 3-kinase (PI-3K)/Akt and p90RSK1 to an extent similar to insulin-like growth factor-1 treatment. In agreement with p90RSK1 activation, E2 also rapidly activated extracellular signal-regulated kinase, and this activity was down-regulated by chemical and biological inhibition of PI-3K suggestive of cross talk between signaling pathways responding to E2. Dominant negative Ras blocked E2-induced BAD phosphorylation and the Raf-activator RasV12T35S induced BAD phosphorylation as well as enhanced E2-induced phosphorylation at S112. Chemical inhibition of PI-3K and mitogen-activated protein kinase kinase 1 inhibited E2-induced BAD phosphorylation at S112 and S136 and expression of dominant negative Ras-induced apoptosis in proliferating cells. Together, these data demonstrate a new nongenomic mechanism by which E2 prevents apoptosis.
Abbreviations used: Dm, double mutant; DN, dominant negative; Wt, wild type.
Online version of this article contains supporting material. Online version is available at www.molbiolcell.org.
* Corresponding author. E-mail address: jwimalas{at}utk.edu.
This article has been cited by other articles:
|
|
 |
|
  U. Telang, D. A. Brazeau, and M. E. Morris Comparison of the Effects of Phenethyl Isothiocyanate and Sulforaphane on Gene Expression in Breast Cancer and Normal Mammary Epithelial Cells Experimental Biology and Medicine, March 1, 2009; 234(3): 287 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Varricchio, A. Migliaccio, G. Castoria, H. Yamaguchi, A. de Falco, M. Di Domenico, P. Giovannelli, W. Farrar, E. Appella, and F. Auricchio Inhibition of Estradiol Receptor/Src Association and Cell Growth by an Estradiol Receptor {alpha} Tyrosine-Phosphorylated Peptide Mol. Cancer Res., November 1, 2007; 5(11): 1213 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ahmad, S. Attoub, M. N. Singh, F. L. Martin, and O. M. A. El-Agnaf {gamma}-Synuclein and the progression of cancer FASEB J, November 1, 2007; 21(13): 3419 - 3430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Fernando, J. S. Foster, A. Bible, A. Strom, R. G. Pestell, M. Rao, A. Saxton, S. J. Baek, K. Yamaguchi, R. Donnell, et al. Breast Cancer Cell Proliferation Is Inhibited by BAD: REGULATION OF CYCLIN D1 J. Biol. Chem., September 28, 2007; 282(39): 28864 - 28873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Naderi, A. E. Teschendorff, J. Beigel, M. Cariati, I. O. Ellis, J. D. Brenton, and C. Caldas BEX2 Is Overexpressed in a Subset of Primary Breast Cancers and Mediates Nerve Growth Factor/Nuclear Factor-{kappa}B Inhibition of Apoptosis in Breast Cancer Cell Lines Cancer Res., July 15, 2007; 67(14): 6725 - 6736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zheng, A. Kallio, and P. Harkonen Tamoxifen-Induced Rapid Death of MCF-7 Breast Cancer Cells Is Mediated via Extracellularly Signal-Regulated Kinase Signaling and Can Be Abrogated by Estrogen Endocrinology, June 1, 2007; 148(6): 2764 - 2777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Urata, Y. Ihara, H. Murata, S. Goto, T. Koji, J. Yodoi, S. Inoue, and T. Kondo 17beta-Estradiol Protects against Oxidative Stress-induced Cell Death through the Glutathione/Glutaredoxin-dependent Redox Regulation of Akt in Myocardiac H9c2 Cells J. Biol. Chem., May 12, 2006; 281(19): 13092 - 13102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pedram, M. Razandi, D. C. Wallace, and E. R. Levin Functional Estrogen Receptors in the Mitochondria of Breast Cancer Cells Mol. Biol. Cell, May 1, 2006; 17(5): 2125 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Vijayanathan, S. Venkiteswaran, S. K. Nair, A. Verma, T.J. Thomas, B. T. Zhu, and T. Thomas Physiologic levels of 2-methoxyestradiol interfere with nongenomic signaling of 17beta-estradiol in human breast cancer cells. Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2038 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamaguchi, S.-H. Lee, J.-S. Kim, J. Wimalasena, S. Kitajima, and S. J. Baek Activating Transcription Factor 3 and Early Growth Response 1 Are the Novel Targets of LY294002 in a Phosphatidylinositol 3-Kinase-Independent Pathway Cancer Res., February 15, 2006; 66(4): 2376 - 2384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sitnick, A. M. Foley, M. Brown, and E. E. Spangenburg Ovariectomy prevents the recovery of atrophied gastrocnemius skeletal muscle mass J Appl Physiol, January 1, 2006; 100(1): 286 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, J. Liu, C. Yu, and A. Lin BAD Ser128 Is Not Phosphorylated by c-Jun NH2-Terminal Kinase for Promoting Apoptosis Cancer Res., September 15, 2005; 65(18): 8372 - 8378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Rodrik, Y. Zheng, F. Harrow, Y. Chen, and D. A. Foster Survival Signals Generated by Estrogen and Phospholipase D in MCF-7 Breast Cancer Cells Are Dependent on Myc Mol. Cell. Biol., September 1, 2005; 25(17): 7917 - 7925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Garcia Palacios, L. J. Robinson, C. W. Borysenko, T. Lehmann, S. E. Kalla, and H. C. Blair Negative Regulation of RANKL-induced Osteoclastic Differentiation in RAW264.7 Cells by Estrogen and Phytoestrogens J. Biol. Chem., April 8, 2005; 280(14): 13720 - 13727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Acconcia, P. Ascenzi, A. Bocedi, E. Spisni, V. Tomasi, A. Trentalance, P. Visca, and M. Marino Palmitoylation-dependent Estrogen Receptor {alpha} Membrane Localization: Regulation by 17{beta}-Estradiol Mol. Biol. Cell, January 1, 2005; 16(1): 231 - 237. [Abstract] [Full Text] [PDF]
|
|
